This is a proposal to investigate mesial-frontal EEG coherence during performance of a Go/No-Go task of motor response inhibition as a biomarker of tic severity and tic suppression in children with Tourette Syndrome (TS). TS is a neuropsychiatric disorder of childhood onset which is characterized by multiple motor and vocal tics. Tics usually appear around 6 years of age, multiply and worsen in number and complexity, and reach the period of worst severity between 10 and 12 years of age. Afterward, tics follow a remitting course in many individuals, remain stable in some or continue to worsen in a minority. Patients who show a remitting course of tics may have successfully developed a compensatory neurobiological mechanism of tic suppression. One study in adults with TS (Serrien et al., 2005) reported increased mesial-frontal EEG coherence in the alpha frequency band during a task of motor response inhibition and it was suggested that this increase represents a mechanism of tic suppression. This study will examine EEG alpha coherence during a task of motor response inhibition in 8 to 12 year old children with TS versus matched unaffected community controls. This proposal builds on the findings of Serrien and colleagues as well as on our own pilot findings of inverse association between EEG alpha coherence and tic severity. In addition, because TS often co-occurs with ADHD, a disorder associated with poor response inhibition, we will also compare children with TS without co-occurring ADHD to children with TS and ADHD. To confirm that the difference between children with TS with and without ADHD is indeed due to ADHD, we will include a control group of children with ADHD without tics. Hence, this is a cross-sectional study involving four groups of subjects: 20 children with TS without ADHD, 20 children with co-occurring TS and ADHD, 20 children with ADHD without tics, and 20 matched healthy community controls. The validation of EEG alpha coherence as a biomarker of tics and tic suppression in this cross-sectional study will create a foundation for developing mechanism-based treatments for TS and for planning longitudinal studies to chart the course of this disorder. PUBLIC HEALTH RELEVANCE: The goal of this study is to examine biomarkers of tic severity and tic suppression in TS, a neuropsychiatric disorder of childhood onset characterized by motor and phonic tics and affecting approximately 0.6 percent of children in the general population. Discovery and validation of biomarkers of tics will promote understanding of a remitting versus a persistent course of TS and the development of mechanism-driven treatments.